Supplemental Figure 3 from EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1

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posted on 2023-03-30, 23:11 authored by Yung-Sheng Chang, Wei-Yu Chen, Juan Juan Yin, Heather Sheppard-Tillman, Jiaoti Huang, Yen-Nien Liu

(A) IF staining of RasB1 and PC3 cells with an antibody for EGFR following EGF and CI1033 treatment. Scale bars represent 50 µm. (B) IHC staining of FFPE cell blocks of RasB1 and PC3 cells with an antibody for p-EGFR (Y1068) following EGF and CI1033 treatment. (C) The intensity of total EGFR was normalized to the internal control, histone 3 or β-actin, from Western blots of nuclear and cytoplasmic cell extracts of RasB1 cells following EGF treatment. (D) The intensity of p-ERK1/2 was normalized to total ERK1/2 from Western blots of nuclear and cytoplasmic cell extracts of RasB1 cells following EGF treatment. (E) ChIP analyses of predicted ATRSs in the pri-miR-1-1 promoter region of 22Rv1 cells following EGF treatment. Enrichment of each protein at each site is given as a percentage of the total input and then normalized to each IgG. Data are presented as the mean {plus minus} SEM, n=3. * vs. -EGF. ** p<0.01, *** p<0.001.

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ARTICLE ABSTRACT

Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis. Cancer Res; 75(15); 3077–86. ©2015 AACR.

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Keywords

Biomarkers Carcinogenesis Signal transduction Gene Regulation Inducible gene expression Genitourinary Cancers Prostate cancer Oncogenes & Tumor Suppressors

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